A number of antigens used in conventional vaccines or proposed for use in future vaccines are relatively poor immunogens especially small protein, peptide or carbohydrate antigens. Such antigens may require conjunction to an immunologic carrier for efficient immunogenicity. The objective of this proposal is to examine the immunologic potential of the hepatitis B virus (HBV) nucleocapsid (HBcAg) to function as a carrier moiety to enhance the immune response to "weak" immunogens such as peptides and carbohydrates. A number of unique immunologic characteristics of Hbcag, and its enhanced immunogenicity in HBV-infected patients suggest that Hbcag may be a superior carrier as compared to conventional protein carriers such as tetanus and diphtheria toxoids. Specifically, heterologous epitopes will be expressed as fusion proteins which assemble into hybrid Hbcag particles or full length protein and carbohydrate antigens will be chemically conjugated to Hbcag. The immunogenicity of the hybrid Hbcag particles will then be compared to conventional hapten-carrier conjugates, and protection from experimental challenge will be determined. Specific projects include: (1) analysis of the T and B cell immune response to Hbcag at a basic level in an attempt to understand its enhanced immunogenicity; (2) the choice of heterologous antigens to be incorporated into hybrid Hbcag particles; (3) the production, purification and chemical-structural analysis of recombinant Hbcag and hybrid Hbcag particles in order to optimize insertion or chemical conjugation of foreign epitopes; (4) antigenic and immunogenic characterization of the hybrid Hbcag particles; and (50 adaptations to allow for oral vaccination such as expression of hybrid Hbcag particles within a Salmonella vector or chemical coupling of hybrid Hbcag particles to the subunit B of E. coli enterotoxin (LT-B). It is anticipated that the performance of these basic and applied studies will permit a rational approach to utilizing Hbcag as a carrier protein in vaccine production for a variety of pathogens requiring T helper cell augmentation.